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ARTICLE TITLE: Clinical Practice Guidelines on the Evidence-Based Use of Integrative Therapies During
and After Breast Cancer Treatment
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Heather Greenlee, ND, PhD, MPH, Melissa J. DuPont-Reyes, MPH, MPhil, Lynda G. Balneaves, RN, PhD, Gary Deng, MD, PhD, Jillian A. Johnson, PhD, Dugald Seely, ND,
MSc, Suzanna Zick, ND, MPH, Lindsay M. Boyce, MLIS, and Debu Tripathy, MD, have no financial relationships or interests to disclose.
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SPONSORED BY THE AMERICAN CANCER SOCIETY, INC.194 VOLUME 67 | NUMBER 3 | MAY/JUNE 2017
1. Highlight current practice guidelines on the use of integrative therapies during and after breast cancer treatment.
2. Apply evidence-based gradings of the efficacy of integrative treatment modalities that balance potential benefits and harms in formulating treatment decisions
and referrals for addressing the symptoms and side effects of breast cancer therapy.
3. Acknowledge the strengths and limitations of integrative therapies for treating breast cancer-related symptoms and side effects and future research needs in this area.
Clinical Practice Guidelines on the Evidence-Based Use of
Integrative Therapies During and After Breast Cancer
Heather Greenlee, ND, PhD, MPH
; Melissa J. DuPont-Reyes, MPH, MPhil
; Lynda G. Balneaves, RN, PhD
Linda E. Carlson, PhD
; Misha R. Cohen, OMD, LAc
; Gary Deng, MD, PhD
; Jillian A. Johnson, PhD
; Matthew Mumber, MD
Dugald Seely, ND, MSc
; Suzanna M. Zick, ND, MPH
; Lindsay M. Boyce, MLIS
; Debu Tripathy, MD
Abstract: Patients with breast cancer commonly use complementary and integrative thera-
pies as supportive care during cancer treatment and to manage treatment-related side
effects. However, evidence supporting the use of such therapies in the oncology setting is
limited. This report provides updated clinical practice guidelines from the Society for Integra-
tive Oncology on the use of integrative therapies for specific clinical indications during and
after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue,
quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphede-
ma, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical prac-
tice guidelines are based on a systematic literature review from 1990 through 2015. Music
therapy, meditation, stress management, and yoga are recommended for anxiety/stress
reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for
depression/mood disorders. Meditation and yoga are recommended to improve quality of
life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced
nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-
induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the
use of ingested dietary supplements to manage breast cancer treatment-related side effects.
In summary, there is a growing body of evidence supporting the use of integrative therapies,
especially mind-body therapies, as effective supportive care strategies during breast cancer
treatment. Many integrative practices, however, remain understudied, with insufficient evi-
dence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232.
VC 2017 American Cancer Society.
Keywords: acupressure, acupuncture, breast cancer, complementary therapies, integrative
medicine, integrative oncology, massage, meditation, music therapy, stress management, yoga
Practical Implications for Continuing Education
> To make informed decisions on the use of integrative therapies in the oncology
setting, clinicians and patients should understand the level of evidence of
associated benefits and harms for each therapy.
> Based on a systematic review of the literature, the Society for Integrative
Oncology makes the following recommendations:
– Use of music therapy, meditation, stress management and yoga for anxiety/
– Use of meditation, relaxation, yoga, massage and music therapy for
– Use of meditation and yoga to improve quality of life.
– Use of acupressure and acupuncture for reducing CINV.
– There is a lack of strong evidence supporting the use of ingested dietary
supplements or botanical agents as supportive care and/or to manage breast
cancer treatment-related side effects.
> Implementing integrative therapies in a clinical setting requires a coordinated
team approach with well-trained providers. Training and credentialing for many
integrative providers varies by jurisdictions. Best practices suggest that
providers be trained to the highest standard of their profession and educated in
other relevant disciplines.
Assistant Professor, Department of
Epidemiology, Mailman School of Public
Health, Columbia University, New York, NY;
Member, Herbert Irving Comprehensive
Cancer Center, Columbia University, New
Doctoral Fellow, Department of
Epidemiology, Mailman School of Public
Health, Columbia University, New York, NY;
Associate Professor, College of Nursing,
Rady Faculty of Health Sciences, Winnipeg,
Professor, Department of
Oncology, University of Calgary, Calgary, AB,
Adjunct Professor, American
College of Traditional Chinese Medicine at
California Institute of Integral Studies, San
Clinic Director, Chicken Soup
Chinese Medicine, San Francisco, CA;
Medical Director, Integrative Oncology,
Memorial Sloan Kettering Cancer Center,
New York, NY;
Department of Biobehavioral Health, The
Pennsylvania State University, University
Radiation Oncologist, Harbin
Clinic, Rome, GA;
Ottawa Integrative Cancer Center, Ottawa,
Executive Director of
Research, Canadian College of Naturopathic
Medicine, Toronto, ON, Canada;
Associate Professor, Department of Family
Medicine, Michigan Medicine, University of
Michigan, Ann Arbor, MI;
Associate Professor, Department of
Nutritional Sciences, School of Public Health,
University of Michigan, Ann Arbor, MI;
Research Informationist, Memorial Sloan
Kettering Library, Memorial Sloan Kettering
Cancer Center, New York, NY;
Department of Breast Medical Oncology, The
University of Texas MD Anderson Cancer
Center, Houston, TX.
Additional supporting information may be
found in the online version of this article.
Corresponding author: Heather Greenlee, ND,
PhD, MPH, Department of Epidemiology, Mailman
School of Public Health, Columbia University, 722
West 168th St, Seventh Fl, New York, NY 10032;
DISCLOSURES: Linda E. Carlson reports book
royalties from New Harbinger and the American
Psychological Association. Misha R. Cohen
reports royalties from Health Concerns Inc.,
outside the submitted work. Matthew Mumber
owns stock in I Thrive. All remaining authors
report no conflicts of interest.
doi: 10.3322/caac.21397. Available online
VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 195
CA CANCER J CLIN 2017;67:194–232
Patients with breast cancer and breast cancer survivors are
frequent users of complementary and integrative therapies,
and there are growing numbers of formal, integrative oncol-
ogy programs within cancer centers.
Various terms are
used to describe such therapies, and it is helpful at the outset
to define terms. Complementary and alternative therapies are
generally defined as any medical system, practice, or product
that is not part of conventional medical care.7,8 Other rele-
vant terminology includes complementary medicine, which
comprises therapies used as a complement alongside
conventional medicine; alternative medicine, which com-
prises therapies used in place of conventional medicine; and
integrative medicine, which is the coordinated use of
evidence-based complementary practices and conventional
care. Integrative oncology refers to the use of complementary
and integrative therapies in collaboration with conventional
oncology care. In oncology, individuals use complementary
and integrative therapies with the intent of enhancing
wellness, improving quality of life (QOL), and relieving
symptoms of disease and side effects of conventional treat-
ments. However, the evidence supporting the use of
complementary and integrative therapies in the oncology
setting is limited.
In November 2014, the Society for Integrative Oncology
(SIO) published clinical practice guidelines to inform both
clinicians and patients on the use of integrative therapies
during breast cancer treatment and to treat breast cancer
treatment-related symptoms.9 The SIO adapted methods
established by the US Preventive Services Task Force10 to
develop graded recommendations on the use of specific inte-
grative therapies for defined clinical indications based on
the strength of available evidence concerning associated
benefits and harms. The 2014 clinical practice guidelines
were derived from a systematic review of randomized clini-
cal trials published between 1990 and 2013 and organized
by specific clinical conditions (eg, anxiety/stress, fatigue).
This review provides an updated set of clinical practice
guidelines based on a current, systematic literature review of
randomized controlled trials (RCTs) published through
December 2015 along with detailed definitions of integra-
tive therapies and clinical outcomes of interest, a detailed
summary of the literature upon which the clinical practice
guidelines are based, and suggestions for how appropriate
therapies may be integrated into clinical practice.
Of note, it is important to define the use of the term rec-
ommendation in these clinical practice guidelines. In many
settings, a clinical guideline recommendation suggests that it
should be used as the standard of care and is favorable or
equal compared with all other options based on best clinical
evidence for benefit/risk ratio. Here, in the setting of inte-
grative oncology, we use the term recommendation to
conclude that the therapy should be considered as a viable
but not singular option for the management of a specific
symptom or side effect. Few studies have conducted a head-
to-head comparison of a given integrative therapy against a
conventional treatment, and most integrative therapies are
used in conjunction with standard therapy and have been
studied in this manner. Moreover, combination-based
approaches and the interactions of the numerous permuta-
tions of integrative and conventional treatments have not
been formally investigated, such that recommendations must
account for this limitation of our knowledge. Despite these
limitations to evaluating the use of integrative therapies in
the oncology setting, there is a body of well conducted trials
of specific therapies for specific conditions that provides suf-
ficient evidence to warrant recommendations on the thera-
pies as viable options for treating specific conditions.
In this review, we provide clinicians and patients with
updated SIO clinical practice guidelines on the use of inte-
grative therapies to manage symptoms and side effects during
and after breast cancer treatment. The clinical practice guide-
lines do not address breast cancer recurrence or survival end-
points, because very few adequately powered RCTs have
examined the effect of integrative therapies on these out-
comes. We also provide a definition for each integrative ther-
apy that had a sufficiently large body of evidence to formulate
a specific recommendation. Information is also provided on
how to implement the recommendations into the clinical set-
ting, with caveats for specific clinical situations. In addition,
this review summarizes pertinent meta-analyses and identifies
promising areas for future investigation. The information
that arose from other published reviews and meta-analyses
did not change the interpretation of the findings or the quali-
ty of specific trials, but the information was used to influence
the establishment of specific recommendation grades based
on consistency, reproducibility, and assessment of potential
harms and benefits. The goal of this current review is to pro-
vide clinicians and patients with practical information and
tools to evaluate whether there is an evidence base to support
the use of a defined integrative therapy for a specific clinical
application in the context of breast cancer.
Systematic Review Methodology
To update the previously published clinical practice guide-
lines, which were based on a systematic review of the litera-
ture from January 1, 1990 through December 31, 2013,
conducted a systematic review of published RCTs from Jan-
uary 1, 2014 through December 31, 2015, using the same
search criteria and process. The process followed the meth-
ods set forth by the Institute of Medicine on clinical guide-
The following databases were searched:
Embase, MEDLINE, PsychINFO, and CINAHL.
Integrative Therapies During and After Breast Cancer Treatment
196 CA: A Cancer Journal for Clinicians
As previously reported,9 trials were selected for inclusion in
the systematic review if they met the following criteria:
1) peer-reviewed, published RCT; 2) available in English;
3) included �50% patients with breast cancer and/or
reported results separately for patients with breast cancer;
4) used an integrative therapy as an intervention during stan-
dard treatment with surgery, chemotherapy, radiation thera-
py, and/or hormonal therapy or addressed symptoms and
side effects resulting from diagnosis and/or treatment; and
5) addressed an endpoint of clinical relevance to patients
with breast cancer and breast cancer survivors (see Support-
ing Information Table 1).9 Several lifestyle and psychological
interventions were excluded from current as well as previous
guidelines, because they have already been well summarized
by other groups (eg, diet
and physical activity
ommendations for cancer survivors) and/or because they
have a strong evidence base and are often considered to be
mainstream rather than integrative or complementary (eg,
and support groups
). Other interventions that were
excluded were in early or pilot stages of research (eg,
attention-restoration therapy) or were not considered to be
an integrative oncology therapy for the purposes of the SIO
guidelines (eg, prayer, spirituality). Each article was scored
according to the quality of design and reporting based on the
Jadad scoring scale and a modified scale adapted from the
Delphi scoring system.18,19 Finally, grades of evidence were
determined for each therapy as applied to a specific clinical
outcome using a modified version of the US Preventive Serv-
ices Task Force grading system.
Grades were based on
strength of evidence, determined by the number of trials,
quality of trials, magnitude of effect, statistical significance,
sample size, consistency of results across studies, and whether
the outcomes were primary or secondary. The highest grades
(A and B) indicate that a specific therapy is recommended for
a particular clinical indication. Grade A indicates there is
high certainty that the net benefit is substantial, while grade
B indicates there is high certainty that the net benefit is mod-
erate or there is moderate certainty that the net benefit is
moderate to substantial. Grade C indicates that the evidence
is equivocal or that there is at least moderate certainty that
the net benefit is small. The lowest grades (D, H, and I) indi-
cate no demonstrated effect, suggest harm, or indicate that
the current evidence is inconclusive, respectively.
According to the clinical guideline development process
outlined by the Institute of Medicine,11 drafts prepared by
the SIO Guideline Working Group were distributed to an
interdisciplinary group of SIO internal and external reviewers.
Reviewer comments, suggestions, and critiques were incorpo-
rated into the final version of these guidelines.
It is important to note that, as we reviewed the literature,
we recognized the difference between statistical and
clinical significance. The graded recommendations reflect
our assessment of the clinical significance based on our
assessment of the body of literature, including the impor-
tance of statistical significance with respect to the primary
endpoint. We did not report on specific magnitudes of
effect because of the range of outcome measures and statisti-
cal methods used across the trials, which made it difficult to
describe detailed data on effect sizes across all trials.
Although some of the trials with small sample sizes (n <
100) may have been methodologically sound, we down-
played their contribution to the graded recommendation,
because larger trials provided more information on general-
izability of results to larger populations. Because of space
limitations, P values are reported and citations are provided
to reference the primary reports for additional details.
Definitions of Complementary and Integrative
Below are definitions listed alphabetically for each of the
complementary and integrative therapies that received
a grade of A, B, C, D, or H in the updated clinical
practice guidelines.20,21 Table 1 displays the graded rec-
Table 2 provides background
information on the specific training, licensure, and profes-
sional organizations associated with each therapy.152 If a
therapy is known to have a specific contraindication or
caution, it is noted in the description. The descriptions
include statements on how the therapies are often used by
patients with cancer and by survivors but do not indicate
the level of evidence supporting such use. The guideline
recommendations provide a summary of the evidence on
the use for specific conditions. In addition to the informa-
tion provided below, there are continuously updated, well
referenced websites that can provide additional details on
the range of therapies, including Natural Medicines (nat-
uralmedicines.therapeuticresearch.com), Memorial Sloan
Kettering Cancer Center’s About Herbs website (mskcc.org/
medicine/herbs), and the National Cancer Institute (NCI)
Office of Cancer Complementary and Alternative Medicine
Therapies: A-Z website (cam.cancer.gov/health_informa-
Acetyl-L-carnitine is a dietary supplement that some
patients use to treat cancer-related fatigue by enhancing
energy and lowering inflammation in the body.
demonstrated effectiveness in preventing and treating dia-
betic neuropathy and thus was of interest to examine in the
context of chemotherapy-induced peripheral neuropathy
(CIPN). It is a substance made in muscle and liver tissue
and is found in foods, including meats, poultry, fish, and
some dairy products.
CA CANCER J CLIN 2017;67:194–232
VOLUME 67 _ NUMBER 3 _ MAY/JUNE 2017 197
TABLE 1. Graded Integrative Therapies for Use in Patients With Breast Cancer According to Clinical Outcomes
OUTCOMES RECOMMENDED THERAPY
Aloe vera22,23 and hyaluronic acid cream24,25 should not be recommended for improving acute
radiation skin reaction.
Anxiety/stress reduction Meditation is recommended for reducing anxiety.26-30 A
Music therapy is recommended for reducing anxiety.31-35 B
Stress management is recommended for reducing anxiety during treatment, but longer group
programs are likely better than self-administered home programs or shorter programs.36-39
Yoga is recommended for reducing anxiety.40-48 B
Acupuncture,49-51 massage,52-55 and relaxation56-60 can be considered for reducing anxiety. C
nausea and vomiting
Acupressure can be considered as an addition to antiemetics drugs to control nausea and
vomiting during chemotherapy.61-63
Electroacupuncture can be considered as an addition to antiemetics drugs to control vomiting
Ginger66-68 and relaxation59,69 can be considered as additions to antiemetic drugs to control
nausea and vomiting during chemotherapy.
Glutamine70,71 should not be recommended for improving nausea and vomiting during
Meditation, particularly MBSR, is recommended for treating mood disturbance and depressive
Relaxation is recommended for improving mood disturbance and depressive
Yoga is recommended for improving mood and depressive symptoms.40-43,45-48,79-85 B
Massage is recommended for improving mood disturbance.53-55,86-88 B
Music therapy is recommended for improving mood.33,35,89,90 B
Acupuncture,49-51,91,92 healing touch,93,94 and stress management36-38,95,96 can be considered
for improving mood disturbance and depressive symptoms.
Fatigue Hypnosis97,98 and ginseng99,100 can be considered for improving fatigue during treatment. C
Acupuncture51,101-103 and yoga45,80,84,104-106 can be considered for improving post-treatment
Acetyl-L-carnitine107 and guarana108,109 should not be recommended for improving fatigue
Lymphedema Low-level laser therapy,110,111 manual lymphatic drainage,112-118 and compression bandag-
ing114-116 can be considered for improving lymphedema.
Neuropathy Acetyl-L-carnitine is not recommended for the prevention of chemotherapy-induced peripheral
neuropathy in patients with BC due to potential harm.107
Pain Acupuncture,119-124 healing touch,93 hypnosis,125,126 and music therapy31,34 can be considered
for the management of pain.
Quality of life Meditation is recommended for improving quality of life.27-29,73-75,127 A
Yoga is recommended for improving quality of life.43,46-48,82-85,104-106,128 B
Acupuncture,49,51,102,129,130 mistletoe,131-134 qigong,135,136 reflexology,137-139 and stress
management36-38,95,96,140,141 can be considered for improving quality of life.
Sleep disturbance Gentle yoga45,48,79,84,142 can be considered for improving sleep. C
Vasomotor/hot flashes Acupuncture49,91,92,143-148 can be considered for improving hot flashes. C
Soy149-151 is not recommended for hot flashes in patients with BC due to lack of effect. D
Abbreviations: BC, breast cancer; MBSR, mindfulness-based stress reduction.